BACKGROUND:The optimal age of kidney transplantation for infants and toddlers with kidney failure is unclear. We aimed to evaluate the patient survival associated with kidney transplantation before 2 years of age versus remaining on the waitlist until ≥2 years. METHOD:We used the Scientific Registry of Transplant Recipients to identify all children added to the deceased-donor waitlist before 2 years of age between 1/1/2000 and 4/30/2020. For each case aged <2 years at transplant, we created a control group comprising all candidates on the waitlist on the case's transplant date. Patient survival was evaluated using sequential Cox regression. Dialysis-free time was defined as graft survival time for cases and the sum of dialysis-free time on the waitlist and graft survival time for controls. RESULTS:We observed similar patient survival for posttransplant periods 0-3 and 4-12 months but higher survival for period >12 months for <2-year decreased-donor recipients (aHR: 0.32; 95% CI: 0.13-0.78; p = .01) compared with controls. Similarly, patient survival was higher for <2-year living-donor recipients for posttransplant period >12 months (aHR: 0.21; 95% CI: 0.06-0.73; p = .01). The 5-year dialysis-free survival was higher for <2-year deceased- (difference: 0.59 years; 95% CI: 0.23-0.93) and living-donor (difference: 1.84 years; 95% CI: 1.31-2.25) recipients. CONCLUSION:Kidney transplantation in children <2 years of age is associated with improved patient survival and reduced dialysis exposure compared with remaining on the waitlist until ≥2 years.

Background:Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease requiring kidney transplantation and can recur in the allograft in 30-80% of recipients resulting in reduced graft survival. Plasmapheresis has shown efficacy in treating some cases of recurrent FSGS but isolated plasmapheresis has not demonstrated efficacy in preventing recurrent FSGS. Rituximab has had anecdotal success in preventing recurrence in a single center study but has not been studied in combination with plasmapheresis for preventing FSGS recurrence.Methods:We are conducting a randomized, controlled, multicenter clinical trial of adult and pediatric kidney transplant recipients with primary FSGS to assess whether plasmapheresis in combination with rituximab prevents recurrent disease post-transplantation.Discussion:Rituximab combined with plasmapheresis is a promising, novel therapy to prevent recurrent FSGS, a disease with limited therapeutic options and no consensus guidelines for prevention or treatment.Clinical trial registration:https://clinicaltrials.gov/ct2/show/NCT03763643, identifier NCT03763643.

EDITORIAL article Front. Pediatr., 23 June 2023Sec. Pediatric Nephrology Volume 11 - 2023 | https://doi.org/10.3389/fped.2023.1221783

Dr John S Najarian (1927-2020), chairman of the Department of Surgery at the University of Minnesota from 1967 to 1993, was a pioneer in surgery, clinical immunology and transplantation. A Covid-delayed Festschrift was held in his honor on May 20, 2022. The speakers reflected on his myriad contributions to surgery, transplantation, and resident/fellow training, as well as current areas of ongoing research to improve clinical outcomes. Of note, Dr Najarian was a founder of the journal Clinical Transplantation.

Background Early in the history of kidney transplantation, short-term graft survival was low. Yet some have had excellent long-term survival. Herein, we describe characteristics of pediatric recipients with > 40 years of graft survival currently alive with a functioning first graft.Methods We reviewed all pediatric (age < 18 years) kidney transplants performed at the University of Minnesota between January 1, 1970, and December 31, 1979 (n = 148), to identify all recipients currently alive with a functioning first graft. Data are presented as medians with interquartile ranges (IQR) and proportions.Results We identified 10 recipients with > 40-year graft survival (median follow-up: 45.0 years (IQR: 43.1, 48.1)). The median age at transplant was 13.8 years (IQR: 5.1, 16.3). All recipients were white; half were male. Of the 10, 4 had glomerulonephritis, 2 had congenital anomalies of the kidney and the urinary tract, 2 had congenital nephrotic syndrome, 1 had Alport syndrome, and 1 had cystic kidney disease as kidney failure cause. Nine patients received a living-related donor transplant, and 1 patient received a deceased-donor transplant. The median estimated glomerular filtration rate at 20 years post-transplant was 79.9 (IQR: 72.3, 98.4); at 30 years, 67.7 (IQR: 63.2, 91.8); and at 40 years, 80.3 ml/min/1.73 m(2) (IQR: 73.7, 86.0). None developed rejection, 5 developed hypertension, 2 developed dyslipidemia, 1 developed diabetes, and 7 patients developed malignancy (4 skin cancer, 2 breast cancer, and 1 post-transplant lymphoproliferative disease).Conclusion Pediatric kidney transplant recipients may achieve > 4 decades of graft survival. Cancer is a common complication warranting vigilant screening.

Background Corticosteroids have been an integral part of maintenance immunosuppression for pediatric kidney transplantation. However, prolonged steroid therapy is associated with significant toxicities resulting in several SW/avoidance strategies in recent years. Method/Objective This comprehensive review aims to discuss steroid-related toxicities and the safety, efficacy, and benefit of steroid avoidance/withdrawal immunosuppression in pediatric kidney transplant recipients. Results Initial studies of SW/avoidance conducted in the setting of CSA and AZA showed an increased incidence of AR but no increase in graft loss or mortality with SW/avoidance maintenance immunosuppression. Studies performed under modern immunosuppression (induction therapy, Tac, and MMF) show no significant increase in AR or graft loss with SW/avoidance immunosuppression. Furthermore, SW/avoidance immunosuppression is associated with significant improvement in growth, BMI, BP control, and lipid profile in pediatric kidney transplant recipients. Despite these data, SW/avoidance remains controversial, and only 40% of pediatric kidney transplant recipients in the United States are currently on SW/avoidance maintenance immunosuppression. Conclusion SW/avoidance maintenance immunosuppression is safe and associated with fewer side effects compared with steroid-inclusive maintenance immunosuppression in pediatric kidney transplant recipients.

We report a kidney transplant recipient in their early twenties with infantile nephropathic cystinosis and EBV viremia who presented with right flank pain, night sweats, and right lower quadrant abdominal tenderness. A CT scan of the abdomen demonstrated mesenteric adenopathy. A laparoscopic mesenteric lymph node biopsy was performed with a concern for post-transplant lymphoproliferative disorder (PTLD). Positive birefringent crystals were identified within the tissue macrophages of benign reactive lymph nodes. Immunohistochemical staining and flow cytometry confirmed polyclonal B-cells without evidence of a clonal B-cell population supportive of PTLD. We report intracellular birefringent crystals within lymph nodes in a patient with infantile cystinosis. We review the clinical history of the patient and the pathologic analysis to evaluate for possible PTLD.

BACKGROUND Registry data from Europe has shown an increase in age at end-stage kidney disease for patients with Alport syndrome in recent years. Whether a similar delay in transplant age has occurred in the United States for Alport patients across all racial/ethnic groups is unknown. MATERIALS AND METHODS We used data from the Scientific Registry of Transplant Recipients (SRTR) to identify 3,794 Alport patients transplanted between 12/1987 and 12/2017. We divided the study period into five equal eras to assess temporal trends in age at transplant, graft survival, and patient survival across racial groups using linear regression and Cox regression models. RESULTS The mean age at transplant for Blacks (28.3 years; difference (Black vs. White): 8.9 years; p < 0.0001) and Hispanics (28.7 years; difference (Hispanics vs. White): 8.7 years; p < 0.0001) was significantly younger compared with that of Whites. We observed a temporal increase in age at transplant for Whites but not for Blacks and Hispanics (p-value for interaction: 0.001). Black recipients were at a higher risk of graft loss (aHR: 1.78; 95% CI: 1.47, 2.15; p < 0.0001) and death (aHR: 1.73; 95% CI: 1.11, 2.69; p = 0.02) compared with White recipients. We observed significant improvements in graft survival with each successive era (p < 0.01). Temporal trends in graft survival (interaction p = 0.46) were not modified by race. CONCLUSION We found racial disparities in age at transplant and long-term graft survival for patients with Alport syndrome in the United States. The age at transplant increased over time for Whites but not Black and Hispanic patients.

Background. Kidneys donated after circulatory death (DCD) are increasingly being used for transplantation in adults to alleviate organ shortage. Pediatric data on survival benefits of DCD transplantation compared with remaining on the waitlist for a kidney donated after brain death (DBD) offer are lacking. Methods. We used Scientific Registry of Transplant Recipients to identify 285 pediatric (<18 y) DCD kidney transplants performed between 1987 and 2017. Propensity score matching was used to create a comparison group of 1132 DBD transplants. We used sequential Cox analysis to evaluate survival benefit of DCD transplantation versus remaining on the waitlist and Cox regression to evaluate patient and graft survival. Results. DCD transplantation was associated with a higher incidence of delayed graft function (adjusted odds ratio: 3.0; P < 0.001). The risks of graft failure (adjusted hazard ratio [aHR], 0.89; P = 0.46) and death (aHR, 1.2; P = 0.67) were similar between DCD and DBD recipients. We found a significant survival benefit of DCD transplantation compared with remaining on the waitlist awaiting a DBD kidney (aHR, 0.44; P = 0.03). Conclusions. Despite a higher incidence of delayed graft function, long-term patient and graft survival are similar between pediatric DCD and DBD kidney transplant recipients. DCD transplantation in children is associated with a survival benefit, despite pediatric priority for organ allocation, compared with remaining on the waitlist.

Journal of the American Society of Nephrology 31(10S):p 710, October 2020. | DOI: 10.1681/ASN.20203110S1710c

Kidney transplantation is the treatment of choice for children with ESKD; however, access to transplantation is limited by the escalating gap between the organ supply and demand. In 2018, only 36% of the 756 pediatric kidney transplants were living donor transplants, indicating that pediatric candidates rely heavily on the deceased donor waiting list. The prevalence of pediatric candidates on the waiting list was 1585 in December 2018 (1). The increase in prevalence is due to a combination of longer waiting times and a decline in deceased donor transplant rates. According to the annual Scientific Registry of Transplant Recipients report, pediatric deceased donor transplant rates declined by 27% from 2009 to 2018 (52/100 versus 37.9/100 waitlist-years). Of the children waitlisted in 2015, 2% died on the waiting list and 15% were still waiting by 2018 (1). Timely transplantation in children is critical for their growth and development. Compared with a functioning graft, dialysis is associated with six times lower patient survival, poorer physical growth, and inferior neurocognitive development (2). Considering the high morbidity and mortality on dialysis, we must explore strategies that would expand the deceased donor pool for children. Despite the severe organ shortage, 20% of kidneys are discarded annually in the United States. In 2019, kidneys from 4460 deceased donors were discarded (3). Of these, 50% were expanded criteria or high kidney donor profile index (KDPI) kidneys (KDPI is a numeric score denoting donor quality based on several donor characteristics), 26% were kidneys donated after cardiac death, and 23% were kidneys at risk of inadvertently transmitting HIV/hepatitis B/hepatitis C to the recipients (3). Other predictors of discard include pediatric donor age, cytomegalovirus seropositivity, hepatitis B/C seropositivity, cigarette use, diabetes, and AB blood type (4). In this article, we review pediatric kidney transplant outcomes associated with kidneys that are …

Pediatric kidney transplant outcomes associated with expanded-criteria donors (ECD) and high Kidney Donor Profile Index (KDPI) kidneys are unknown. We reviewed the Scientific Registry of Transplant Recipients data from 1987-2017 to identify 96 ECD and 92 > 85 KDPI kidney recipients (<18 years). Using propensity scores, we created comparison groups of 375 non-ECD and 357 ≤ 85 KDPI recipients for comparisons with ECD and > 85 KDPI transplants, respectively. We used Cox regression for patient/graft survival and sequential Cox approach for survival benefit of ECD and > 85 KDPI transplantationvs remaining on the waitlist. After adjustment, ECD recipients were at significantly increased risk of graft failure (adjusted hazard ratio [aHR] = 1.6; P = .001) but not of mortality (aHR = 1.33; P = .15) compared with non-ECD recipients. We observed no survival benefit of ECD transplants vs remaining on the waitlist (aHR = 1.05; P = .83). We found no significant difference in graft failure (aHR = 1.27; P = .12) and mortality (aHR = 1.41; P = .13) risks between > 85 KDPI and ≤ 85 KDPI recipients. However, > 85 KDPI transplants were associated with a survival benefit vs remaining on the waitlist (aHR = 0.41; P = .01). ECD transplantation in children is associated with a high graft loss risk and no survival benefit, whereas > 85 KDPI transplantation is associated with a survival benefit for children vs remaining on the waitlist.

BACKGROUND:En bloc transplantation of small pediatric kidneys in children may help expand the existing deceased donor pool; however, studies examining the long-term outcomes of en bloc transplantation in children are few.METHODS:We used the Scientific Registry of Transplant Recipients to identify 149 pediatric en bloc recipients transplanted from October 1, 1987 to December 31, 2017. We used propensity scores to match 148 en bloc with 581 non-en bloc deceased donor recipients (matching variables: transplant age, gender, race, pretransplant dialysis, transplant center, and year). We evaluated patient and graft survival using Kaplan-Meier and Fleming-Harrington weighted log-rank test and examined survival benefit of en bloc transplantation versus remaining on the waiting list using the sequential Cox approach. We divided the study period into three 10-y intervals to assess the effect of era on outcomes.RESULTS:Compared with non-en bloc recipients, en bloc recipients had lower 1-y graft survival (78.9% versus 88.9%; P = 0.007); however, when stratified by transplant era, lower 1-y survival was only observed in the oldest era (1987-1997). En bloc recipients had superior 10-y patient (89.0% versus 80.4%; P = 0.04) and graft survival (51.6% versus 39.9%; P = 0.04) compared with non-en bloc recipients. After multivariate adjustment, en bloc transplantation was associated with superior patient survival compared with remaining on the waiting list (adjusted hazard ratio: 0.58; 95% confidence interval: 0.36-0.95; P = 0.03).CONCLUSIONS:En bloc transplantation of small pediatric kidneys in children is associated with superior long-term patient and graft survival. The increased risk of 1-y graft loss among en bloc recipients only appeared in the oldest era.

Temporal changes in kidney transplant outcomes for cystinosis are unknown. We used the SRTR to identify all kidney transplants performed for cystinosis in patients younger than 31 years between 1987 and 2017. We divided time into three equal eras (1987-1997, 1998-2007, and 2008-2017) to assess changes in outcomes using Cox proportional and linear regression models. We examined 441 transplants in 362 patients. Age at ESRD progressively increased (12.1 vs 13.3 vs 13.4; P = .046). Eras 2 and 3 had lower risk of acute rejection (aHR 2 vs 1:0.45; P < .001) (aHR 3 vs 1:0.26; P < .001) and higher 5-year mean GFR (difference 2 vs 1:9.2 mL/min/1.73 m(2); P = .005) (difference 3 vs 1:12.9 mL/min/1.73 m(2); P = .002) compared with era 1. Five-year graft survival was similar across eras, but 5-year patient survival was higher for era 2 (aHR: 0.25; P = .01). Seventy-nine patients underwent retransplantation. Five-year patient (94.2% vs 92.5%; P = .57) and graft survival (79.1% vs 74.1%; P = .52) were similar between primary and subsequent transplants. Age at ESRD, acute rejection, GFR at 5 years, and patient survival improved over time. Kidney retransplantation is associated with excellent outcomes in children and young adults with cystinosis.

Increased risk donors (IRDs) may inadvertently transmit blood-borne viruses to organ recipients through transplant. Rates of IRD kidney transplants in children and the associated outcomes are unknown. We used the Scientific Registry of Transplant Recipients to identify pediatric deceased donor kidney transplants that were performed in the United States between January 1, 2005 and December 31, 2015. We used the Cox regression analysis to compare patient and graft survival between IRD and non-IRD recipients, and a sequential Cox approach to evaluate survival benefit after IRD transplants compared with remaining on the waitlist and never accepting an IRD kidney. We studied 328 recipients with and 4850 without IRD transplants. The annual IRD transplant rates ranged from 3.4% to 13.2%. IRDs were more likely to be male (P = .04), black (P < .001), and die from head trauma (P = .006). IRD recipients had higher mean cPRA (0.085 vs 0.065, P = .02). After multivariate adjustment, patient survival after IRD transplants was significantly higher compared with remaining on the waitlist (adjusted hazard ratio [aHR]: 0.48, 95% CI: 0.26-0.88, P = .018); however, patient (aHR: 0.93, 95% CI: 0.54-1.59, P = .79) and graft survival (aHR: 0.89, 95% CI: 0.70-1.13, P = .32) were similar between IRD and non-IRD recipients. We recommend that IRDs be considered for transplant in children.

Background. Infants (age, < 2 years) with end-stage renal disease (ESRD) have increased morbidity and mortality. We evaluated our long-term outcomes of kidney transplants (KTx) in infants. Methods. Between 1984 and 2014, 136 infants underwent KTx. We examined trends in survival rates and complications by era (1984-1993 [era 1], 1994-2003 [era 2], 2004-2014 [era 3]). Results. Patients were 92.6% white and 70.6% males. Posttransplant (Tx) initial length of hospital stay declined 37% over the 30-year period (P < 0.01). Ten-year death-censored graft survival improved from 60% (era 1) to 80% (era 2) (P = 0.04). The incidence of acute rejection, graft thrombosis, cytomegalovirus, and urine leaks did not significantly change across eras. Frequency of Epstein-Barr virus diagnosis (era 2 vs era 3, P < 0.01) increased. Post-Tx lymphoproliferative disorder incidence was increased in era 2 compared with eras 1 and 3 (P = 0.03). Conclusions. Infants deserve earlier consideration for KTx. Length of initial hospital stay and patient and graft survival rates after KTx have improved in infants since 1984.

In this single-center retrospective study, we analyzed kidney transplant outcomes in nine pediatric patients with VACTERL [vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities] association-making this the largest study of its kind. Of 743 pediatric kidney transplant recipients at our center (1980-2017), nine had documented diagnoses of VACTERL association. All nine had congenital anorectal malformations and renal anomalies, five had vertebral defects, and one had a bifid thumb and tracheoesophageal fistula. Renal anomalies included dysplasia (n = 6), aplasia (n = 3), and horseshoe kidney (n = 2). Congenital lower urinary tract anomalies included neurogenic bladder (n = 6), obstructive uropathy (n = 4), anovesicular fistula (n = 1), rectourethral fistula (n = 1), and posterior urethral valves (n = 1). Age at transplant ranged from 1.2 to 15 years (mean, 7.3; standard deviation [SD], 5.5); 6 (67%) were male, and 3 (33%) were female; 6 (67%) had a living related donor, and 3 (33%) had a deceased donor. The overall graft survival rate was 78% (range, 1.5 to 25.2 years; mean, 10.5; SD, 8.9). One month post-transplant, one recipient died with a functioning graft. At 3.7 years post-transplant, one graft failed because of recurrent pyelonephritis. Post-transplant urologic complications included pyelonephritis (n = 6), vesicoureteral reflux (n = 5), and graft hydronephrosis (n = 4). We conclude that pediatric patients with VACTERL association can be safely transplanted-careful patient selection with vigilance and intervention for pre- and post-transplant urologic complications is essential.

Background KT recipients have increased the risk of CVD. The incidence of post-transplant CVEs among pediatric recipients has not been well-characterized. Patients and MethodsResultsBetween 1963 and 2015, 884 pediatric (age: 0-17years old) recipients received 1058 KTs at our institution. The cumulative incidence of CVEs was analyzed. Statistical models were used to estimate risk factors for developing post-transplant CVEs. Overall median patient survival was 33years (IQR: 18.7-47). A total of 362 CVEs occurred in 161 (18.3%) patients at a median age of 20.5years. Arrhythmias (18%) were most common. Cumulative risk of post-transplant CVEs was 9% at 10years, 17% at 20years, 25% at 30years, and 36% at 40years. Development of post-transplant CVEs was associated with increased mortality (HR 2.25 [95% CI 1.61-3.14]); of those who developed a CVE and died, 22/51 (43.1%) died of CVD. Multivariable risk factors for post-transplant CVEs included a history of pretransplant CVD (aHR 1.92 [1.18-3.13] and graft failure (4.57 [3.13-6.67]). DiscussionA pretransplant history of CVD and a failed graft are significant risk factors for the development of post-transplant CVE. CVD increases the risk of post-transplant death or graft loss.

In adults on chronic hemodialysis, achieving a hemoglobin concentration of 12g/dl and above with erythropoiesis stimulating agents leads to increased cardiovascular events and mortality, but this may not be true in children. Therefore, we conducted a retrospective cohort study of pediatric patients (under 18) from the Centers for Medicare and Medicaid Services End Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) project (2000 to 2008) merged with the United States Renal Data System. Hemoglobin was determined from the Clinical Performance Measures data, and beginning annually on January 1st of the next year, patients were followed for up to 1 year. We determined the outcomes (mortality, hospitalization, and cardiovascular events) during follow-up by hemoglobin group at baseline. Models were adjusted for demographic and clinical characteristics of 1569 children studied. The hemoglobin 12 g/dl and above group was older, had fewer years of ESRD, and was more often transplanted. Inpatient and outpatient visits for congestive heart failure, cardiomyopathy, and valvular heart disease were most common in the hemoglobin under 10g/dl group and the frequency of these diagnoses decreased with increasing hemoglobin. The hazard ratio of all-cause mortality (0.33, 95% confidence interval 0.14-0.81) and the adjusted relative rate of all-cause hospitalizations (0.81, 0.74-0.89) were significantly lower in the hemoglobin 12 g/dl and above group. Cardiovascular hospitalizations were significantly higher in the hemoglobin under 10g/dl group (1.31, 1.05-1.64). Thus, in children on hemodialysis, hemoglobin 12g/dl and above is not associated with increased cardiovascular visits, mortality, or all-cause and cardiovascular-related hospitalizations.

AR is lower in pKTx recipients on Tac vs CsA. Data comparing infection outcomes for children treated with these agents are limited. We retrospectively studied infection outcomes in 96 pKTx recipients on a RDP. PS, DCGS, AR, and infection-free survival were assessed using Kaplan-Meier/log-rank tests and proportional hazards models. There were no differences in 1-year PS, DCGS, or AR between Tac and CsA recipients. After adjusting for AR, the hazard of CMV viremia was 4.0 times higher (95% CI: 1.04, 15.5; P = .044) and that of BK viremia was 3.8 times higher (95% CI: 1.5, 10.2; P = .007) in Tac recipients. The incidence of EBV viremia was similar between the groups (P = .56). PostTx lymphoproliferative disease was only observed in Tac recipients (3%). There was no difference in the incidence of pneumonia, urinary tract, or Clostridium difficile infections between Tac and CsA recipients. Among KTx recipients on RDP, the hazards of CMV and BK viremia within 1 year post-KTx were significantly higher in Tac recipients compared to CsA. Regular assessment for infections and lower Tac trough levels may be warranted in Tac recipients.